1. Field of the Invention
This invention relates to new chemical compounds and more particularly to novel bicyclic azolo[1,3]diazepine derivatives.
2. Description of the Prior Art
In a recent publication by Chan et al, J. Org. Chem., 1982, 47, 3457, the synthesis of the potent adenosine deaminase inhibitor pentostatin, (i.e., 8(R)-3-(2-deoxy-.beta.-D-erythro-pentofuranosyl)-3,6,7,8-tetrahydroimidazo [4,6-d][1,3]diazepin-8-ol) with the following structure, compound 1, ##STR2## and structurally related to the natural product coformycin, compound 2, was disclosed. Thus, it is now known that pentostatin, 1, like coformycin, 2, are exceedingly tight binding inhibitors of human erythrocytic adenosine deaminase, exhibiting Ki=1.times.10.sup.-12 M and Ki=1.times.10.sup.-11 M, respectively. In combination with 9-.beta.-D-arabinofuranosyl adenine, pentostatin has shown dramatic antitumor effects both in vitro and in vivo. However, the acute renal toxicity of pentostatin in clinical trials (see, Mitchell et al, R. Blood, 1980, 56, 556 and Cancer Treat. Rep., 1979, 63, 1439) has initiated a search for other (see Baker et al, J. Org. Chem., 1982, 47, 2179) strong inhibitors of the enzyme which might lack these unfortunate side effects.